This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Patients with type 1 diabetes and symptoms of abdominal fullness, bloating, distention and nausea are usually considered to have autonomic neuropathy. Limitations of staining methods have presented pathological confirmation of this diagnosis and restricted research. We have used immunohistochemical methods to stain unmyelinated epidermal nerves in skin for many years. Using these methods on stomach and jejunum of diabetic patients we discovered degeneration of enteric mucosal nerves, dilated blood vessels, and hypertrophic enterocytes. The affected nerves are mainly afferents that provide the sensory input about lumen contents to the brain and spinal cord for modulation of peristaltic and secretory reflexes. We believe that this is the first histological confirmation of autonomic neuropathy. We propose to study mucosal nerves of the stomach in type I candidates for pancreas transplantation to further charcterize our initial findings, to develop specific criteria for diagnosis of neuropathy, and to quantify entercyte hypertrophy. We will also determine whether epidermal nerves can act as surrogates for diagnosis of enteric nerve pathology. In addition to diagnosis, the results will provide new information about the innervation of the normal and diabetic stomach, lead to better understanding of the neural basis of abnormal accomodation, delayed gastic emptying and fluctuating hypo- and hyperglycemia, and stimulate research in this field. This research should lead to better patient understanding of the factors that complicate blood glucose control thereby leading to improved management. We hope the research will stimulate development of instruments to promote scheduled gastric emptying as a means to prevent hypoglycemia. It can also provide surgeons with knowledge of the motility potential of operated diabetic intestine for more rational therapy of postoperative intestinal stasis.